rs587779741

Variant names:

• chr6-156778207-A-T
• rs587779741
• NM_001374828.1:c.527A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001374828.1(ARID1B):​c.527A>T​(p.His176Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H176Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0890
• Publications: 1 publications found

Genes affected

ARID1B (HGNC:18040): (AT-rich interaction domain 1B) This locus encodes an AT-rich DNA interacting domain-containing protein. The encoded protein is a component of the SWI/SNF chromatin remodeling complex and may play a role in cell-cycle activation. The protein encoded by this locus is similar to AT-rich interactive domain-containing protein 1A. These two proteins function as alternative, mutually exclusive ARID-subunits of the SWI/SNF complex. The associated complexes play opposing roles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ARID1B Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, ClinGen, Orphanet
• Coffin-Siris syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17060816).
• BP6: Variant 6-156778207-A-T is Benign according to our data. Variant chr6-156778207-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 126321.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374828.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.527A>T	p.His176Leu	missense	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.527A>T	p.His176Leu	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.527A>T	p.His176Leu	missense	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.527A>T	p.His176Leu	missense	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.527A>T	p.His176Leu	missense	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.527A>T	p.His176Leu	missense	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386990 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 684472

African (AFR) AF: 0.00 AC: 0 AN: 31518

American (AMR) AF: 0.00 AC: 0 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25164

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35700

South Asian (SAS) AF: 0.00 AC: 0 AN: 79140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4996

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077496

Other (OTH) AF: 0.00 AC: 0 AN: 57782

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.32	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.089
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.065
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.069	T
Polyphen		0.20	B
Vest4		0.21
MVP		0.25
MPC		0.36
ClinPred		0.43	T
GERP RS		2.5
PromoterAI		0.0054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.27
gMVP		0.41
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587779741; hg19: chr6-157099341;